Regulatory T‐cell phenotype in association with large cell transformation of mycosis fungoides

Abstract

Transformation of MF to high grade lymphoma may be associated with the adoption of a regulatory T-cell phenotype. FOXP3 expression may contribute to aggressive behavior of MF after large cell transformation via immune escape mechanism. The significance of this observation is limited by the low case number in this study.

Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma

“…This finding agrees with other published studies that indicate that FoxP3 protein is not expressed to any significant degree by neoplastic cells in skin lesions or peripheral blood of most patients with MF/SS whereas the cutaneous infiltrates do have variable proportions of tumor-infiltrating FoxP3+ cells [62][63][64][65]. In recent study, Gjerdrum evaluated FoxP3 protein expression in 69 patients with MF further classified into early patch/plaque (n = 10), infiltrated plaque (n = 42), non-transformed tumor (n = 10), and transformed tumor (n = 7) cases [65].…”

“…This study also found that FoxP3 protein was not expressed by neoplastic cells in the skin infiltrate in any of these cases although it should be noted that negative FoxP3 staining was defined as absent or less than 10% staining by neoplastic cells, suggesting that occasional neoplastic cells could have been positive. Interestingly, the lack of FoxP3 protein in transformed MF in this study differs from the experience of Hallermann in which 4 of 5 cases of CD30+ transformed MF cases expressed FoxP3 [64]. The reason for this discrepancy is unclear but could be due to technical reasons (immunohistochemistry with or without antigen retrieval; FoxP3 antibody clones 236A/E7 versus hFoxy) [66].…”

“…However, an alternative explanation is that FoxP3 mRNA may be easier to detect by the more sensitive qPCR technique than FoxP3 protein by standard methods which would account for the apparent lack of FoxP3 protein by neoplastic cells in most tissue samples and CTCL-derived cells lines. If so, an increased amount of FoxP3 protein detected by immunohistochemistry occurs in only certain unusual circumstances such as large cell transformation [64].…”

FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival

“…[35][36][37][38][39] One recent study has indicated that transformation of MF to CD30-positive large T-cell lymphomas is associated with a Treg phenotype. 40 However, the limited number of cases investigated (n ¼ 5) and the lack of controls for the immunolabelling restricts the interpretation of this study.…”

Regulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome

“…[52][53][54] Similarly, a study using the controversial hFOXY anti-FOXP3 antibody found that four patients with non-transformed MF were FOXP3-negative but that the malignant T cells in four of five patients with transformed MF expressed FOXP3 indicating that transformation of MF to a high-grade lymphoma is associated with adoption of a Treg phenotype. 55 However, FOXP3 þ malignant T cells were not detected when sections from the same patients were subsequently stained with three distinct FOXP3-specific antibodies. 56 In a larger study, Gjerdrum et al 57 did observe a sub-population of FOXP3 þ malignant T cells in 6 of 86 patients with CTCL of which 69 had MF and 17 CTCL unspecified.…”